Yole D S, Pemberton R, Reid G D, Wilson R A
Institute of Primate Research, Karen, Nairobi, Kenya.
Parasitology. 1996 Jan;112 ( Pt 1):37-46. doi: 10.1017/s0031182000065057.
The radiation-attenuated schistosome vaccine induces a high level of protective immunity in rodents. In order to assess its potential relevance to man, we have tested its efficacy in the non-human primate Papio anubis. A vaccination regime consisting of 3 exposures of approximately 9000 cercariae irradiated with 30 or 60 krad. of gamma radiation induced > 50% protection to a challenge with normal larvae. A lower attenuating dose of 20 krad., optimal for vaccination of mice, was less effective. All vaccination regimes elicited a population of PBMC which proliferated in vitro in response to antigen. These responses peaked after the third exposure but were significantly lower after challenge. They revealed relatively little cross-reactivity with adult Schistosoma haematobium antigens and provided some evidence for stage-specific antigens. Circulating IgM reactive with adult S. mansoni antigen was detected after the second vaccination but levels remained low throughout. In contrast, IgG levels were boosted by successive vaccinations, although they showed a tendency to decline from 14 days after each exposure. There also appeared to be a lag of about 14 days after challenge before levels began to rise. Thus, both proliferation and antibody data suggest a lower responsiveness after challenge which may reflect either the reduced antigenic load or immunogenicity of normal, compared to vaccinating larvae. The data indicate that the attenuated schistosome vaccine is capable of inducing protection in a highly permissive primate host, with the implication that the mechanisms involved may also be relevant to man.
辐射减毒血吸虫疫苗可在啮齿动物中诱导高水平的保护性免疫。为评估其对人类的潜在相关性,我们在非人灵长类动物埃及狒狒中测试了其效力。一种接种方案包括3次暴露,每次暴露约9000条经30或60千拉德γ辐射照射的尾蚴,该方案可使动物对正常幼虫攻击产生>50%的保护作用。对小鼠接种而言最佳的20千拉德较低减毒剂量效果较差。所有接种方案均引发了一群外周血单核细胞(PBMC),这些细胞在体外对抗原产生增殖反应。这些反应在第三次暴露后达到峰值,但在攻击后显著降低。它们与埃及血吸虫成虫抗原的交叉反应相对较少,并为阶段特异性抗原提供了一些证据。第二次接种后检测到与曼氏血吸虫成虫抗原反应的循环IgM,但水平始终较低。相比之下,IgG水平通过连续接种而升高,尽管每次暴露后14天显示有下降趋势。攻击后似乎也有约14天的滞后时间,之后水平才开始上升。因此,增殖和抗体数据均表明攻击后反应性较低,这可能反映了与接种幼虫相比,正常幼虫的抗原负荷或免疫原性降低。数据表明,减毒血吸虫疫苗能够在高度易感的灵长类宿主中诱导保护作用,这意味着其中涉及的机制可能也与人类相关。